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Biliary excretion of ioglycamide was studied in Wistar and Gunn rats. A hepatic transport-maximum (Tm) was observed. Higher Tm-values were found in Gunn rats, which have a greater bile flow compared to the parent Wistar rats, in spite of having a similar bile acid output. This suggests that the Tm is related to the bile acid-independent bile flow. In bile acid-depleted Wistar rats, bile acid output was 30% of control values whereas bile flow and ioglycamide-Tm had only decreased by approximately 15%. Ioglycamide excretion could not be increased by taurocholate infusion. An additional 22.0 ml of bile was excreted per mmol of biliary ioglycamide. Loads of the contrast agent markedly exceeding the Tm resulted in a decrease of its own biliary excretion and its choleretic properties. These presumed 'toxic' effects were counteracted by near-physiological amounts of taurocholate. Thus, the effect of taurocholate varies greatly depending upon the amounts of the contrast agent and the taurocholate administered.

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The bile acid taurocholate increases the biliary excretion of organic anions, such as sulfobromophthalein (BSP), bilirubin and iopanoic acid. In the present study has been investigated the effect of taurocholate on 1. Canine biliary excretion and concentration of the i.v. contrast medium ioglycamide and 2. Canine bile flow. The experimental model consisted of cholecystectomized, anaesthetized dogs with a fistula, through which the common bile duct could be catheterized and drained. One hour after cannulation, i.v. infusion of ioglycamide at a rate of 4 mumol/min./kg. was started. Two hours after the infusion start a control group received i.v. infusion of saline, while in another a 1.5% sodium taurocholate infusion was started with stepwise increases with 30 min. intervals from 0.4 to 0.8, 1.6 and 3.2 mumol/min./kg. Compared with control, all rates of taurocholate infusion increased bile flow and decreased biliary ioglycamide concentration. Although the bile flow with increasing taurocholate infusion rates was enhanced, the biliary ioglycamide excretion did not increase. The results indicate that ioglycamide and taurocholate are excreted into bile by separate excretion mechanisms. As taurocholate increases the biliary excretion of some other organic anions, it supports the hypothesis that organic anions are excreted into bile by more than two excretion mechanisms, taurocholate affecting only some of them.

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Theophylline (TH), which has been shown in experimental dogs to increase bile-salt-independent bile flow, was studied in its effect on the biliary excretion and concentration of the intravenous contrast medium ioglycamide in cholecystectomized anesthetized dogs equipped with a Thomas cannula through which the common bile duct could be cannulated. One hour after cannulation, i.v. infusion of ioglycamide at the rate of 4 mol/min/Kg was started. Two hours later, 10 mg/kg of TH was injected intravenously and the experiment continued for a further 75 minutes. Bile was collected at 15 min. intervals throughout the whole experiment and simultaneous intravenous blood samples were taken. In this study, TH increased bile flow and decreased biliary ioglycamide concentration. Although TH increased bile flow, it had no effect on the biliary excretion of ioglycamide. It may be postulated that the organic anion ioglycamide, and possibly other organic anions, are secreted into the bile by mechanisms, unaffected by drugs which increase bile-salt-independent bile flow in a similar manner to TH.

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The effect of furosemide on biliary excretion of ioglycamide and bile flow during experimental cholangiography was studied in cholecystectomized and anaesthetized dogs equipped with a Thomas cannula through which the common bile duct could be cannulated. Ioglycamide infusion was started one hour after cannulation of the common bile duct, the infusion rate being 4 micromol/min/kg. Two hours later, 2 mg/kg furosemide was injected intravenously. After furosemide administration biliary ioglycamide concentration and bile flow remained the same as before the furosemide administration. Our evidence suggests that furosemide has no effect on the biliary excretion of ioglycamide or bile flow during ioglycamide cholangiography on dogs.

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The concentration of iodine in the bile of patients with indwelling T-tubes has been measured following administration of the new cholangiographic agent Iotroxamide. Studies have been performed after administration of the contrast agent by both 10 min bolus injection and 1 h drip infusion techniques. Comparison has been made with the iodine concentrations obtained after administration of equimolar amounts of Ioglycamide. There was no significant difference in the biliary iodine levels obtained with the two methods of administration when Iotroxamide was the contrast agent employed. However, with Ioglycamide the slow infusion technique produced higher iodine levels than the bolus injection method (P less than 0.05). Comparison between the two agents reveals that, whichever administration technique is used, Iotroxamide provides higher iodine levels than Ioglycamide. After bolus injection the superiority for Iotroxamide is in the region of 20% and after slow infusion is of the order of 10--15%. It is concluded that Iotroxamide is likely to prove superior to Ioglycamide as a cholangiographic agent. In terms of opacification of the biliary tree there is little to choose between bolus injection and slow infusion techniques when using Iotroxamide and the relative toxicity of the two techniques should be the major factor in determining which method is employed in clinical practice.

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The present study reports on the effect of glucagon on the excretion of ioglycamate in experimental intravenous cholangiography on dogs. Glucagon increased the bile flow rate highly significantly (p < 0.001). At the same time the concentration of the contrast medium decreased highly significantly (p < 0.001). The biliary tree output of the contrast medium also increased, this increase was not statistically significant. This investigation suggests that glucagon seems to have effect on the bile flow as well as on the output of contrast medium in experimental cholangiography.

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The effect of atropine on the bile flow and biliary excretion of ioglycamate, a biliary contrast medium, was studied on four anesthetized mongrel dogs equipped with a Thomas cannula through which the common bile duct was cannulated. With an infusion rate of 2 microgram/kg/min atropine sulphate decreased bile flow significantly. At the same time, the biliary concentration of ioglycamate was significantly increased. The biliary output of ioglycamate did not change during atropine infusion. The present study suggests that in this experimental model atropine decreases the bile flow but does not affect the excretion of ioglycamate.

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Iodine-131 labelled Biligram has been evaluated as a radiopharmaceutical for dynamic scintiscanning of the liver and biliary tract. In 10 normal subjects there was good visualisation of the liver and gallbladder. In 18 patients 131I Biligram was found to be unsatifactory for differentiating parenchymal liver disease from biliary tract obstruction owing to inability to demonstrate the gallbladder when liver function was more than mildly deranged. Quantitative analyses of blood clearance and hepatic activity curves for 131I Biligram were not clinically helpful. Urinary excretion of 131I Biligram increased with the degree of hepatic dysfunction.

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In the anaesthetized pig we studied the influence of the dosage of the contrast medium Iotroxinate on the following parameters of bile secretion: bile flow, bile salt excretion, concentration, and excretion of Iotroxinate. The results demonstrate that high doses of Iotroxinate inhibit the bile salt independent fraction of bile flow in a dose-dependent manner, by analogy to organic anions like Rose Bengal, Indocyaningreen, Ioglycamite. The biliary concentration of Iotroxinate however increases slightly. That means, that high doses of Iotroxinate do not impair the quality of opacification of bile ducts in x-ray examinations, as the contrast medium concentration represents the decisive parameter for a valid cholegraphy.

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Biliary excretion of iotroxamat (ITX) and ioglycamide (IGL) in cholecystectomized dogs fitted with a Thomas duodenal cannula is compatible with saturation kinetics exhibiting maximal excretory velocities of 2.23 +/- SD 0.18 and 1.22 +/- 0.19 mumol/min/kg, respectively. While biliary excretion of ITX obeyed classical Michaelis Menten kinetics, the data obtained with IGL suggested a more complex process. The choleretic effects of both contrast agents (23.6 +/- SD 2.29 and 25.8 +/- 2.21 microliter of excreted substance) were comparable. On the basis of these results and in view of the similar toxicity of the two contrast agents in animals, it may be expected that ITX will have advantages over IGL for intravenous cholangiography.

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Twenty-one anicteric patients with a t-tube in situ were studied between the ninth and 11th postoperative days. Eleven patients were given an intravenous infusion of the biliary contrast agent ioglycamide (Biligram), while the other 10 acted as controls. Bile flow was recorded and the biliary concentrations of ioglycamide, bile salt, phospholipid, and cholesterol estimated in the two groups. The biliary excretion of ioglycamide was associated with a significant choleresis which was probably due to the obligatory coupling of the osmotically active contrast agent molecules with water. Biliary ioglycamide excretion did not significantly alter bile salt secretion rates. In contrast, the biliary secretion of both phospholipid and cholesterol was significantly lowered (P less than 0.001). Unlike chenodeoxycholic acid, ioglycamide significantly reduced bile acid independent cholesterol secretion (P less than 0.01), although secretion rate in terms of mumol of bile acid was essentially unchanged.

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When five patients with varying degrees of hepatic impairment and a T-tube in situ were given intravenous ioglycamide at a rate of 2 mg/kg/min for two hours the mean biliary excretion in the first two hours was only 3.2% of the administered dose. In contrast, in five T-tube patients with relatively normal liver function the mean biliary excretion over the same time interval was 20.6%. The mean plasma concentration of ioglycamide achieved at the end of a two-hour intravenous infusion at 2 mg/kg/min was 1427 +/- 187 microgram/ml in six anicteric patients and 1262 +/- 82 in six jaundiced patients. Despite these very similar plasma levels the 24-hour urinary excretion of ioglycamide was 42.3 +/- 3.8% of the administered dose in the patients with jaundice compared with only 18.1 +/- 2.4% in the anicteric group. These differences probably reflect the fact that the percentage of unbound contrast agent in the plasma of the jaundiced group (11.9 +/- 1.9%) was significantly higher than that of the anicteric group (6.4 +/- 0.9%). It is suggested that bilirubin and possibly other substances in the plasma are competing with ioglycamide for binding sites on albumin. These factors need to be borne in mind when performing intravenous cholangiograms on jaundiced patients.

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Plasma ioglycamide concentration was linearly related to the rate of intravenous infusion over a dose range of from 1 to 4 mg per kg per min. The relation between plasma and biliary concentration of ioglycamide was studied in 15 anicteric patients with a T-tube in situ. Peak biliary concentrations and excretory rates of ioglycamide were seen when the plasma concentration was greater than 1500 micrograms per ml. The mean biliary transport maximum (Tm) for ioglycamide in man was 31.6 mg/min (range 22.0-40.4). The results suggest that near optimal concentrations of iodine in the bile duct can be obtained during intravenous cholangiography if ioglycamide is infused for one hour at a rate of about 4 mg per kg per min.

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The distribution and biliary excretion of two hepatotropic contrast media, Ioglycamate and Iotroxinate, has been studied in the anaesthetized pig in infusion experiments. The new substance Iotroxinate exceeds the Ioglycamate in two of the investigated parameters: it was excreted faster and reached a higher biliary concentration. The biliary transport maximum, however, was unchanged. On the basis of these experiments the new contrast medium Iotroxinate was tested in men.

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The binding relationships between ioglycamide and steroid hormones were determined in a liquid two-phase system with labelled ioglycamide and by direct measurement of ultraviolet light absorption. It was found that an interaction between ioglycamide and steroid hormones, particularly progesterone, existed, relative to the binding to human serum protein.

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Loops of small intestine in seven rabbits were resected with intact pedicle and ligated at both ends after instillation of 0.5 ml of Gastrografin, Urografin 76%, Amipaque 370 mg I/ml, Amipaque 170 mg I/ml or physiologic saline. After half an hour, the amount of fluid in the loops containing Gastrografin and Urografin 76% increases about twice as much as in the loops containing Amipague with the same iodine concentration because of their greater osmolality. The differences between the loops with isotonic Amipaque (170 mg I/ml) and physiologic saline are not significant. Precipitation occurs when sodium and meglumine salts of diatrizoate, metrizoate, iothalamate, iocarmate and ioglycamate are mixed with 0.05 N HCl. No precipitation occurs with Amipaque, not even when the HCl concentration is as high as 1.2 N. Precipitation occurs when Gastrografin is added to gastric juices with low pH, but is not seen with Amipaque should be a suitable contrast medium for gastrointestinal examinations because of its low osmolality and toxicity and good solubility in gastric juice.

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